Biomaterial Database

Physiologically-based toxicokinetic modeling of durene (1,2,3,5-tetramethylbenzene) and isodurene (1,2,4,5-tetramethylbenzene) in humans. 2007

Piotr Jałowiecki, and Beata Janasik

Department of Biological Monitoring, Nofer Institute of Occupational Medicine, Łódź, Poland. pjalowiecki@mors.sggw.waw.pl

OBJECTIVE Physiologically-based toxicokinetic (PB-TK) models are developed to simulate absorption, distribution and excretion of xenobiotics. PB-TK models consist of several groups of compartments, where tissues are grouped together according to physiological parameters (tissue blood flows, tissue group volumes) and physicochemical properties (partition coefficients, metabolic constants). Tetramethylbenzene (TETMB), a mixture of its three isomers: prenitene (1,2,3,4-TETMB), isodurene (1,2,3,5-TETMB), and durene (1,2,4,5-TETMB) is an essential component of numerous commercial preparations of organic solvents. The aim of the study was to develop the PB-TK model for two TETMB isomers, durene and isodurene, in humans. METHODS The assumed PB-TK model groups organs and tissues into five physiological compartments: fat tissue, muscles, organs, liver, and brain. The brain has been considered as a separate compartment due to the potential neurotoxicity of TETMB. Water/air, oil/air and blood/air partition coefficients for durene and isodurene were measured in vitro. Tissue/air partition coefficients were calculated from values of olive/air and water/air partition coefficients and the average fat and water content in different tissues. Tissue/blood partition coefficients were calculated as a tissue/air quotient and the blood/air partition coefficient measured in vitro. The Michaelis-Menten constant (KM) values and maximum metabolism rate constant (VMAX) for selected metabolites of durene and isodurene were obtained in vitro using microsomal fraction of the human liver. RESULTS The developed model was validated against experimental data obtained earlier as a result of an 8-h exposure of volunteers to durene and isodurene vapors of 10 and 25 mg/m3. The prediction of both TETMB isomers concentration in blood as well as of the elimination rates of 2,4,5-TMBA and 2,3,5-TMBA were close to the results of experimental exposures. CONCLUSIONS Simulations of one working week inhalation exposure to aromatic hydrocarbons indicate that the elaborated PB-TK model may be used to predict the chemical distribution in different body compartments, based on physicochemical properties.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D008954	Models, Biological	Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.	Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D008958	Models, Molecular	Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.	Molecular Models,Model, Molecular,Molecular Model
D011044	Poland	A country in central Europe, east of Germany. The capital is Warsaw.	Polish People's Republic,Republic of Poland
D002849	Chromatography, Gas	Fractionation of a vaporized sample as a consequence of partition between a mobile gaseous phase and a stationary phase held in a column. Two types are gas-solid chromatography, where the fixed phase is a solid, and gas-liquid, in which the stationary phase is a nonvolatile liquid supported on an inert solid matrix.	Chromatography, Gas-Liquid,Gas Chromatography,Chromatographies, Gas,Chromatographies, Gas-Liquid,Chromatography, Gas Liquid,Gas Chromatographies,Gas-Liquid Chromatographies,Gas-Liquid Chromatography
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006841	Hydrocarbons, Aromatic	Organic compounds containing carbon and hydrogen in the form of an unsaturated, usually hexagonal ring structure. The compounds can be single ring, or double, triple, or multiple fused rings.	Aromatic Hydrocarbon,Aromatic Hydrocarbons,Hydrocarbon, Aromatic
D000280	Administration, Inhalation	The administration of drugs by the respiratory route. It includes insufflation into the respiratory tract.	Drug Administration, Inhalation,Drug Administration, Respiratory,Drug Aerosol Therapy,Inhalation Drug Administration,Inhalation of Drugs,Respiratory Drug Administration,Aerosol Drug Therapy,Aerosol Therapy, Drug,Drug Therapy, Aerosol,Inhalation Administration,Administration, Inhalation Drug,Administration, Respiratory Drug,Therapy, Aerosol Drug,Therapy, Drug Aerosol
D000328	Adult	A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available.	Adults
D001555	Benzene Derivatives	Organic compounds derived from BENZENE.	Derivatives, Benzene